Thermal, kinetic, spectroscopic studies and anti-microbial, anti-tuberculosis, anti-oxidant properties of clioquinol and benzo-coumarin derivatives mixed complexes with copper ion

Article abstract of DOI:10.1007/s00044-013-0576-6

A series of six Cu(II) complexes of clioquinol with benzo-coumarin derivatives have been synthesized. Physico-chemical, spectroscopic, and thermal properties of the complexes have been studied on the basis of infrared spectra, mass spectra, NMR spectra, e

Full text of DOI:10.1007/s00044-013-0576-6

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-013-0576-6
ORIGINAL RESEARCH
Thermal, kinetic, spectroscopic studies and anti-microbial, anti-
tuberculosis, anti-oxidant properties of clioquinol and benzo-
coumarin derivatives mixed complexes with copper ion
•
Hitesh R. Dholariya Ketan S. Patel
•
•
Jiten C. Patel Atul K. Patel Kanuprasad D. Patel
•
Received: 4 January 2013 / Accepted: 5 March 2013
Ó Springer Science+Business Media New York 2013
Abstract A series of six Cu(II) complexes of clioquinol
with benzo-coumarin derivatives have been synthesized.
Physico-chemical, spectroscopic, and thermal properties of
the complexes have been studied on the basis of infrared
spectra, mass spectra, NMR spectra, electronic spectra,
elemental analyses, and thermogravimetric analyses. The
kinetic parameters such as order of reaction (n), energy of
activation (Ea), entropy (S*), pre-exponential factor (A),
enthalpy (H*), and Gibbs free energy (G*) have been cal-
culated using Freeman-Carroll method. All the compounds
were screened for their anti-bacterial activity against Esch-
erichia coli, Pseudomonas aeruginosa, Streptococcus
pyogenes, Bacillus subtilis, and anti-fungal activity against
Candida albicans and Aspergillus niger. Ferric-reducing
anti-oxidant power of all complexes were measured. Also the
compounds against Mycobacterium tuberculosis showsclear
enhancement in the anti-tubercular activity upon copper
complexation.
Abbreviations
CQ
L
Clioquinol
L1, L2, L3, L4, L5, L6
L1
L2
2-Cinnamoyl-3H-benzo[f]chromen-3-one
(E)-2-(3-(3-Hydroxyphenyl)acryloyl)-3H-benzo[f]
chromen-3-one
L3
L4
L5
L6
(E)-2-(3-(4-Hydroxyphenyl)acryloyl)-3H-benzo[f]
chromen-3-one
(E)-2-(3-(4-Chlorophenyl)acryloyl)-3H-benzo[f]
chromen-3-one
(E)-2-(3-(4-Nitrophenyl)acryloyl)-3H-benzo[f]
chromen-3-one
(E)-2-(3-(2-Nitrophenyl)acryloyl)-3H-benzo[f]
chromen-3-one
C
C1, C2, C3, C4, C5, C6
C1
C2
C3
C4
C5
C6
[Cu(L1)(CQ)(H2O)(OH)]
[Cu(L2)(CQ)(H2O)(OH)]
[Cu(L3)(CQ)(H2O)(OH)]
[Cu(L4)(CQ)(H2O)(OH)]
Keywords Benzo-coumarin derivative ꢀ Cu(II) complex ꢀ
Anti-microbial ꢀ Anti-oxidant ꢀ Anti-tuberculosis
[Cu(L5)(CQ)(H2O)(OH)]
[Cu(L6)(CQ)(H2O)(OH)]
B.M. Bohr magneton
TG Thermo gravimetry
DTG Differential thermogravimetric
Ea
A
Activation energy
Pre-expontial factor
Order of reaction
Electronic supplementary material The online version of this
article (doi:10.1007/s00044-013-0576-6) contains supplementary
material, which is available to authorized users.
N
H. R. Dholariya ꢀ K. S. Patel ꢀ J. C. Patel ꢀ
A. K. Patel ꢀ K. D. Patel (&)
Introduction
V. P. & R. P. T. P. Science College, Sardar Patel University,
Vallabh Vidyanagar 388 120, Gujarat, India
e-mail: drkdpatel64@yahoo.co.in
Interest in coumarin chemistry has flourished for numerous
years, largely as a result of extensive increase in the use of
coumarin derivatives. Naturally occurring as well as synthetic
coumarin derivatives find applications in various therapeutic
H. R. Dholariya
e-mail: hitesh.msc123@gmail.com
123

Med Chem Res
areas (Olomola et al., 2010; Riveiro et al., 2010). Coumarin is
a widely occurring secondary metabolite that occurs naturally
in several plant families and essential oils, and has been used
as sweeteners, fixatives of perfumes, additives in food, and
cosmetics, odor stabilizers in tobacco and odor maskers in
paints and rubber (Tyagi et al., 2005). In addition, heterocy-
clic compounds containing coumarin synthon have shown
various activities such as anti-HIV, (Bedoya et al., 2005;
Kirkiacharian et al., 2002; Lee, 2003; Thaisrivongs et al.,
1994) anti-coagulant, (Kidane et al., 2004) anti-bacterial,
(Khan et al., 2004) anti-cancer, (Radanyi et al., 2008)
anthelminthic, (Lee et al., 1998) anti–inflammatory, (Ghate
et al., 2003; Kontogiorgis and Hadjipavlou-Litina, 2004), and
anti-oxidant (Kontogiorgis and Hadjipavlou-Litina, 2004;
Nicolaides et al., 1998; Raj et al., 1998). The nature of sub-
stituent classifies that coumarin substitution at positions-3 is
dominant for anti-microbial activity (Debeljak et al., 2007).
Due to the known anti-microbial activity (Dawara and Singh,
2011; Hishmat et al., 1989; Kharadi and Patel, 2010), we were
interested to prepare 3-acetyl coumarin derivatives and its
metal complexes.
Although effective natural defense mechanisms against these
highly reactive species exist (e.g., natural anti-oxidants such
as vitamins E and C, b-carotene, and polyphenolic flavo-
noids), excessive ROS production which escorts many path-
ophysiological conditions (oxidative stress) poses the need of
further anti-oxidant protection. As a result, research for the
development of novel small molecules with anti-oxidant
activity is constantly attracting attention. Hence, our effort is
focused on these metal-ion complexes because of their
promising uses as anti-oxidant agents (Colak et al., 2010).
The aim of this study was to prepare the mixed-ligand
complexes of Cu(II) using CQ with coumarin derivatives
and to determine their properties. In our previous reports,
we have mentioned a series of fused coumarin derivatives
and its transition metal complexes (Kharadi and Patel,
2009a; b). In continuation of our preceding work, we
describe here synthesis, characterization, and spectroscopic
features of new mixed-ligand Cu(II) complexes of CQ
with coumarin derivatives along with anti–microbial, anti–
oxidant, and anti–tubercular activities. Thermal behavior of
the complexes has been investigated using thermogravi-
metric (TG) analysis. Thermogravimetry is a process in
which a substance is decomposed in the presence of heat,
which causes bonds of the molecules to be broken (Albano
et al., 2000; Carrasco, 1993). Kinetic parameters like order
of reaction (n), activation energy (Ea), entropy change (S*),
enthalpy change (H*), free energy change (G*), and pre-
exponential factor (A) are carried out using kinetic studies
of thermal decomposition reactions.
Derivative of 8-hydroxyquinoline i.e., clioquinol (CQ) is
well-known for their anti-biotic properties in therapy due to
its coordinating ability towards metal ions. CQ derivatives,
especially 5-chloro-7-iodo-8-hydroxyquinoline (CQ) atten-
uated Alzheimer’s disease (AD) symptoms in human clinical
trials, belonging to the family of drugs called anti-infectives.
CQ is an anti-bacterial and anti-fungal agent, which used
widely as a topical cream for the treatment of skin infections
such as eczema, athlete’s foot, and other fungal infections
(Ritchie et al., 2003; Yassin et al., 2000). Inciting renewed
interest in its pharmacodynamics and linking its possible
advantageous therapeutical action to the chelation of cop-
per(II) in the brain. Metal ions and complexes have key roles
in a broad range of processes necessary for brain function
(Burdette and Lippard, 2003). Cu(II) plays a significant role
in brain metabolism, as it is essential for the known enzymes
CuZn, superoxide dismutase (SOD), ceruloplasmin, cyto-
chrome C-oxidase, tyrosinase and dopamine b-hydroxylase.
Copper is also associated with various biomolecules related
to essential physiological activities in human organism.
Until now numerous researches have been actively investi-
gated copper compounds based on the hypothesis that
endogenous metals may prove less toxic and more potent
(Marzano et al., 2009). It has been well-established that the
properties of copper complexes are largely determined by the
nature of ligands and the donor atoms bound to the metal ion.
Redox activity of Cu(II) ion plays a decisive role in
addressing the main effects of this metal. Cu(II) may con-
tribute to the production of free radicals and in regulation and
in induction of apoptosis (Kozlowski et al., 2009).
Experimental
Material
All chemicals were purchased from the following com-
mercial sources: Spectrochem Pvt. Ltd., Mumbai, E. Merck
Pvt. Ltd., Mumbai, S D Fine Chem Limited, Mumbai. All
chemicals were of reagent grade and solvents of analytical
grade were distilled, purified and dried using appropriate
methods (Vogel and Furniss, 1989). All reactions were
monitored by thin-layer chromatography (TLC on alu-
minium plates coated with silica gel 60 F254, 0.25 mm
thickness, Merck) and detection of the components were
done under UV light or explore in iodine chamber. The
metal nitrates were used in hydrated form.
Physical measurement
Elemental analysis was performed by elemental analyzer
PerkinElmer, Cambridge, MA, USA 2400-II CHN. Analyses
of metal ions was carried out by the dissolution of the solid
complexes in hot concentrated nitric acid, further diluted
Reactive oxygen species (ROS) are formed by aerobic
organisms as an unavoidable consequence of cell metabolism.
123

Med Chem Res
2-Cinnamoyl-3H-benzo[f]chromen-3-one (L1)
with distilled water (DW) and filtered to remove the pre-
cipitated organic ligands. Remaining solution was neu-
tralized with ammonia solution and the metal ions were
titrated against EDTA. Melting points were measured
using open capillary. Infrared spectra were recorded in the
region of 4,000–400 cm-1 on Shimadzu FTIR 8401
A mixture of 2-acetyl-3H-benzo[f]chromen-3-one (0.01 mol)
and benzaldehyde (0.015 mol) in chloroform (50 mL) was
taken in 100 mL round bottomed flask fitted with a reflux
condenser. Catalytic amount of piperidine (1.0 mL) was
added and the reaction mixture was stirred for 10 min at
room temperature. After clear solution obtained mixture
was refluxed for 6 h and progress of the reaction was
monitored by TLC. After completion of reaction (as evi-
denced by TLC), the reaction mixture was cooled to room
temperature. A solid product separated out was filtered out,
washed with cold ethanol and dried in air. It was recrys-
tallized from ethanol–DMF (9:1) mixture. C22H14O3: yield,
80 %; m.p. 207 °C. ESI–MS (m/z): 326.3[M]?. Found
1
spectrophotometer using KBr pellets. H and 13C NMR
measurements were carried out on Avance-II 400 Bruker
NMR spectrometer. Chemical shifts were measured with
respect to TMS as internal standard and DMSO-d6 used as
solvent. FAB mass spectrums of complexes were recorded
at CDRI, Lucknow with JEOL SX-102/DA-6000 mass
spectrometer at room temperature using Argon/Xenon as
the FAB gas. Electronic spectra were recorded on a
LAMBDA 19 UV/VIS/NIR in the region of 200–1,200 nm.
TG scans were run on a model Diamond TG/DTA, Perk-
inElmer, Cambridge, MA, USA. The analysis carried out
under a nitrogen atmosphere at a heating rate of
20 °C min-1 from 30 to 840 °C. Effective magnetic sus-
ceptibility measurement were calculated by the Gouy’s
method using mercury tetrathiocyanatocobaltate (II) as
1
(%): C, 80.71, H, 4.03. Calculated: C, 80.97, H, 4.32; H
NMR (DMSO-d6 400 MHz): d: 7.46–7.82 (10H, m, Ar–H
and H12), 8.06 (1H, d, J = 7.8 Hz, Ar–H9), 8.30 (1H, d,
J = 9.0 Hz, H13), 8.62 (1H, d, J = 8.2 Hz, Ar–H5), 9.35
(1H, s, Ar–H4); 13C NMR (DMSO-d6 100 MHz): d: 112.61
(C-4a), 116.33 (C-10), 122.27, 123.84, 124.49, 126.35,
128.57, 128.90, 128.97, 129.30, 129.86, 130.66, 134.44,
135.92 (14C, Ar–C), 142.79 (C-14), 143.81 (C-13), 151.22
(C-4), 155.17 (C-10a), 158.42 (C=O, lactone carbon of
coumarin), 186.64 (C=O, a, b-unsaturated ketone); FTIR
(KBr cm-1): 1610 (C=O, a, b-unsaturated ketone), 1722
(C=O, lactone carbonyl of coumarin).
a
calibrant (v = 16.44 9 10-6 c.g.s. units at 20 °C).
Molar susceptibility was corrected using Pascal’s constant
(Mabbs and Machin, 2008).
Preparation of ligands
2-Acetyl-3H-benzo[f]chromen-3-one was prepared accord-
ing to reported method (Bischler, 1892). General procedure
for the synthesis of ligands (L) is shown in Scheme 1.
In a 250 mL three-neck round bottom flask, a mixture of
2-hydroxynaphthaldehyde (0.1 mol) and ethylacetoacetate
(0.1 mol) was taken in 50 mL ethanol. Catalytic amount of
piperidine (3–4 drops) was added and the reaction mixture
was stirred for 10 min at room temperature. It was further
heated for 2 h; in water bath. A yellow solid obtained was
separated by filtration, washed with cold ether and dried
over the vacuum pump. It was recrystallized from chloro-
form–hexane. Yield, 85 %; m.p. 189 °C. ESI–MS (m/z):
238.8 (M)?.
(E)-2-(3-(3-Hydroxyphenyl)acryloyl)-3H-
benzo[f]chromen-3-one (L2)
L2 was synthesized by the same method used for L1 using
3-hydroxybenzaldehyde. C22H14O4: yield, 76 %; m.p.
252 °C. ESI–MS (m/z): 342.6[M]?. Found (%): C, 77.48,
H, 4.42 %. Calculated: C, 77.18, H, 4.12; 1H NMR
(DMSO-d6 400 MHz): d: 6.87–7.79 (9H, m, Ar–H and
H12), 8.08 (1H, d, J = 8.0 Hz, Ar–H9), 8.31 (1H, d,
J = 9.2 Hz, Ar–H13), 8.63 (1H, d, J = 8.4 Hz, Ar–H5),
9.30 (1H, s, Ar–H4), 9.71 (1H, br s, Ar–OH); 13C NMR
(DMSO-d6 100 MHz): d: 112.63 (C-4a), 114.48 (C-10),
Scheme 1 General procedure for synthesis of ligands (L)
123

Med Chem Res
116.48, 118.16, 120.11, 122.45, 124.10, 124.54, 126.46,
128.98, 129.02, 129.25, 129.85, 130.06, 135.73 (13C,
Ar–C), 135.87 (C-14), 142.56 (C-13), 144.12 (C-4), 155.06
(C-10a), 157.75 (C–OH), 158.48 (C=O, lactone carbon of
coumarin), 186.99 (C=O, a, b-unsaturated ketone); FTIR
(KBr cm-1): 3380 (O–H, -stretching), 1610 (C=O, a, b-
unsaturated ketone), 1743 (C=O, lactone carbonyl of
coumarin).
ESI–MS (m/z): 371.3[M]?. Found (%): C, 71.37, H, 3.74,
1
N, 3.98. Calculated: C, 71.16, H, 3.53, N, 3.77; H NMR
(DMSO-d6 400 MHz): d: 6.90–7.65 (9H, m, Ar–H and
H12), 8.15 (1H, d, J = 8.4 Hz, Ar–H9), 8.25 (1H, d,
J = 9.6 Hz, Ar–H13), 8.47 (1H, d, J = 8.0 Hz, Ar–H5),
9.38 (1H, s, C4–H); 13C NMR (DMSO-d6 100 MHz): d:
111.73 (C-4a), 114.20 (C-10), 116.69, 118.34, 120.91,
122.65, 124.65, 126.76, 128.08, 129.22, 129.95, 130.35,
135.13 (13C, Ar–C), 135.89 (C-14), 143.16 (C-13), 144.52
(C-4), 147.42 (C-17, carbon attach to NO2), 155.46 (C-
10a), 159.28 (C=O, lactone carbon of coumarin), 187.29
(C=O, a, b-unsaturated ketone); FTIR (KBr cm-1): 1608
(C=O, a, b-unsaturated ketone), 1735 (C=O, lactone car-
bonyl of coumarin), 1510 (Ar–NO2, asymmetric), 1345
(Ar–NO2, symmetric).
(E)-2-(3-(4-Hydroxyphenyl)acryloyl)-3H-
benzo[f]chromen-3-one (L3)
L3 was synthesized by the same method used for L1 using
4-hydroxybenzaldehyde. C22H14O4: yield, 78 %; m.p. 259 °C.
ESI–MS (m/z): 342.8[M]?. Found (%): C, 77.42, H, 4.38.
Calculated: C, 77.18, H, 4.12; 1H NMR (DMSO-d6
400 MHz): d: 6.81–7.92 (9H, m, Ar–H and H12), 8.21 (1H,
d, J = 8.8 Hz, Ar–H9), 8.42 (1H, d, J = 9.6 Hz, Ar–H13),
8.75 (1H, d, J = 8.0 Hz, Ar–H5), 9.42 (1H, s, C4–H), 9.89
(1H, s, –OH); 13C NMR (DMSO-d6 100 MHz): d: 111.64
(C-4a), 114.87 (C-10), 117.54, 120.76, 122.64, 124.69,
124.87, 126.12, 128.62, 129.56, 129.94, 130.23, 135.46
(13C, Ar–C), 136.32 (C-14), 143.54 (C-13), 146.12 (C-4),
155.06 (C-10a), 157.56 (C–OH), 159.24 (C=O, lactone
carbon of coumarin), 187.09 (C=O, a, b-unsaturated
ketone); FTIR (KBr cm-1): 3385 (O–H, -stretching), 1615
(C=O, a, b-unsaturated ketone), 1740 (C=O, lactone car-
bonyl of coumarin).
(E)-2-(3-(2-Nitrophenyl)acryloyl)-3H-
benzo[f]chromen-3-one (L6)
L6 was synthesized by the same method used for L1 using
2-nitrobenzaldehyde. C22H13NO5: yield, 65 %; m.p. 218 °C.
ESI–MS (m/z): 371.6[M]?. Found (%): C, 71.42, H, 3.76,
1
N, 3.96. Calculated: C, 71.16, H, 3.53, N, 3.77; H NMR
(DMSO-d6 400 MHz): d: 6.80–7.20 (9H, m, Ar–H and
H12), 7.80 (1H, d, J = 8.8 Hz, Ar–H9), 8.05 (1H, d,
J = 10.4 Hz, Ar–H13), 8.18 (1H, d, J = 8.4 Hz, Ar–H5),
9.23 (1H, s, C4–H); 13C NMR (DMSO-d6 100 MHz): d:
111.73 (C-4a), 113.56 (C-10), 116.67, 118.86, 120.31,
122.68, 124.21, 124.25, 126.87, 128.78, 129.42, 129.35,
132.55, 133.06, 134.28 (13C, Ar–C), 135.65 (C-14), 142.32
(C-13), 144.56 (C-4), 152.22 (C-15, carbon attach to phe-
nolic NO2), 155.26 (C-10a), 158.44 (C=O, lactone carbon
of coumarin), 186.39 (C=O, a, b-unsaturated ketone); FTIR
(KBr cm-1): 1605 (C=O, a, b-unsaturated ketone), 1738
(C=O, lactone carbonyl of coumarin), 1495 (Ar–NO2,
asymmetric), 1330 (Ar–NO2, symmetric).
(E)-2-(3-(4-Chlorophenyl)acryloyl)-3H-
benzo[f]chromen-3-one (L4)
L4 was synthesized by the same method used for L1 using
4-chlorobenzaldehyde. C22H13ClO3: yield, 68 %; m.p.
230 °C. ESI–MS (m/z): 360.5[M]?, 362.2[M?2]?. Found
(%): C, 73.59, H, 3.93. Calculated: C, 73.24, H, 3.63; 1H NMR
(DMSO-d6 400 MHz): d: 7.43–7.85 (9H, m, Ar–H and H12),
8.18 (1H, d, J = 8.0 Hz, Ar–H9), 8.45 (1H, d, J = 10.0 Hz,
Ar–H13), 8.63 (1H, d, J = 8.8 Hz, Ar–H5), 9.38 (1H, s, C4–
H); 13C NMR (DMSO-d6 100 MHz): d: 113.23 (C-4a), 114.44
(C-10), 115.48, 118.54, 122.21, 124.65, 125.19, 125.84,
126.46, 127.28, 128.35, 130.46, 133.5, 134.23 (14C, Ar–C),
135.67 (C-14), 142.46 (C-13) 144.42 (C-4), 155.36 (C-10a),
158.68 (C=O, lactone carbon of coumarin), 186.49 (C=O, a,
b-unsaturated ketone); FTIR (KBr cm-1): 1605 (C=O, a,
b-unsaturated ketone), 1725 (C=O, lactone carbonyl of
coumarin), 1090 (p-substituted (C–Cl)).
Synthesis of complexes (C1–C6)
All these complexes (C1–C6) were prepared by the general
experimental procedure as described below and synthetic
route of complexes (C) shown in Scheme 2.
A hot ethanolic solution of hydrated metal nitrate i.e.,
Cu(NO3)2ꢀ3H2O (1.0 mmol) and ligand (L) (1.0 mmol) was
slowly added to a ethanolic solution of CQ (1.0 mmol). The
resultant mixture was neutralized (pH = 7) using dilute
solution of NaOH in water. Furthermore, the mixture was
heated under reflux for 6–8 h; after that solution was
evaporated to half of its original volume. The formed pre-
cipitates were filtered off, washed with ethanol followed by
diethyl ether and dried under vacuum. The physico-chem-
ical data of the synthesized complexes are listed in Table 1.
(E)-2-(3-(4-Nitrophenyl)acryloyl)-3H-
benzo[f]chromen-3-one (L5)
L5 was synthesized by the same method used for L1 using
4-nitrobenzaldehyde. C22H13NO5: yield, 64 %; m.p. 244 °C.
123

Med Chem Res
Scheme 2 General synthetic
route of complexes (C)
Table 1 Analytical and physiochemical parameters of the complexes
Entry Empirical formula
Elemental analyses, % found (required)
m.p.
(°C)
Yield
(%)
Molecular
mass
leff
B.M.
C
H
N
Cu(II)
C1
C2
C3
C4
C5
C6
[Cu(L1)(CQ)(H2O)(OH)]
C31H21ClCuINO6
51.37 (51.05) 2.73 (2.90) 1.59 (1.92) 8.93 (8.71) [300
49.73 (49.95) 2.66 (2.84) 1.69 (1.88) 8.81 (8.53) [300
49.67 (49.95) 2.69 (2.84) 1.63 (1.88) 8.37 (8.53) [300
48.52 (48.74) 2.88 (2.64) 1.57 (1.83) 8.61 (8.32) [300
48.35 (48.08) 2.82 (2.60) 3.50 (3.62) 8.52 (8.21) [300
48.42 (48.08) 2.84 (2.60) 3.48 (3.62) 8.47 (8.21) [300
75
72
77
72
65
62
727.47
743.65
743.72
761.44
772.75
772.51
1.91
1.88
1.90
1.93
1.92
1.87
[Cu(L2)(CQ)(H2O)(OH)]
C31H21ClCuINO7
[Cu(L3)(CQ)(H2O)(OH)]
C31H21ClCuINO7
[Cu(L4)(CQ)(H2O)(OH)]
C31H20Cl2CuINO6
[Cu(L5)(CQ)(H2O)(OH)]
C31H20ClCuIN2O8
[Cu(L6)(CQ)(H2O)(OH)]
C31H20ClCuIN2O8
The complexes comprise high melting points ([300 °C)
and are insoluble in common organic solvents but partially
soluble in DMF as well as DMSO.
and anti-fungal drugs were prepared in DMSO. The results
including standard drugs are summarized in Table 2.
In this method, anti-biotics are impregnated onto paper
disks and then placed on a seeded Mueller–Hinton agar
plate using a mechanical dispenser or sterile forceps. Plate
is then incubated for 16–18 h at 37 °C and diameter of zone
of inhibition around disk is measured to the nearest milli-
meter. Solution of all newly synthesized compounds and
standard drugs were prepared at 600, 400, 200, 100, 70, 40,
20 lg mL-1 and at 100, 80, 60, 40, 35, 30, 20, 15, 10, 5, 2,
1 lg mL-1 concentrations, respectively using micro dilu-
tion method, in the wells of microplates by plating in MHB.
The lowest concentration of compound that completely
inhibits macroscopic growth was determined and minimum
inhibitory concentrations (MIC) are reported in Table 2.
Method of anti-microbial assay
The minimum inhibition concentration (MIC) of synthe-
sized compounds was carried out using Kirby-Bauer disk
diffusion method according to the guidelines of Clinical and
Laboratory Standards Institute (CLSI) (Clinical and Labo-
ratory Standards Institute (Clsi) (formerly Nccls) Perfor-
mance Standards for Anti-microbial Disk Susceptibility
Tests Approved Standard, 2006). Anti-bacterial activity
was screened against two Gram-positive (B. subtilis ATCC
11774, S. pyogenes ATCC12384) and two Gram-negative
(E. coli ATCC 25922, P. aeruginosa ATCC 25619) bacteria
by taking ciprofloxacin and norfloxacin as standard anti-
bacterial drugs. Anti-fungal activity was screened against
two fungal species (C. albicans ATCC 66027 and A. niger
ATCC64958), where flucanazole and nystatin were used as
standard anti-fungal drugs. All ATCC cultures were col-
lected from Bangalore and tested against above-mentioned
known drugs. The standard solutions of anti-bacterial drugs
Method of anti-oxidant assay
Ferric-reducing anti-oxidant power (FRAP) was measured
by a modified method (Parmar et al., 2012). The anti-
oxidant potentials of compounds were estimated as their
power to reduce the TPTZ–Fe(III) complex to TPTZ–Fe(II)
complex. This method is simple, fast, and reproducible
results can be obtained. Total anti-oxidant capacity of
123

Med Chem Res
Table 2 Anti-microbial and anti-oxidant activities of synthesized compounds
Anti-microbial activity (minimal inhibition concentration, in lg mL-1
)
Anti-oxidant activity
FRAP value (mmol 100 g-1
)
Entry
Gram-negative bacteria
Gram-positive bacteria
Fungus
E. coli
P. aeruginosa
S. pyogenes
B. subtilis
C. albicans
A. niger
L1
400
400
200
100
100
200
100
100
70
400
200
200
100
200
400
100
100
100
70
400
200
400
100
100
200
100
100
100
40
[600
600
400
200
200
400
100
200
100
40
400
200
200
200
200
400
200
100
100
100
100
100
NT
NT
NT
10
200
200
400
200
200
200
100
100
100
100
100
100
NT
NT
NT
10
NT
NT
NT
NT
NT
NT
332
402
367
306
335
353
NT
NT
NT
NT
NT
L2
L3
L4
L5
L6
C1
C2
C3
C4
40
C5
70
100
200
100
10
70
100
200
100
05
C6
100
100
20
100
100
20
Ampicillin
Ciprofloxacin
Norfloxacin
Flucanazole
Nystatin
10
10
10
10
NT
NT
NT
NT
NT
NT
NT
NT
100
100
E. Coli = ATCC25922; P. aeruginosa = ATCC25619; S. pyogenes = ATCC12384; B. subtilis = ATCC11774; C.albicans = ATCC 66027;
A. niger = ATCC 64958
NT not tested
biological samples is expressed as ascorbic equivalent
(mmol 100 g-1 of dried compound).
interpreted for M. tuberculosis H37Rv according to the
procedure of the approved micro dilution reference method
of anti-microbial susceptibility testing (Akhaja and Raval,
2011; Andrew, 2001; Rattan and Churchill, 2000). Com-
pounds were taken at concentrations of 100, 50, 25, 12.5,
6.25, and 3.125 lg mL-1 in DMSO, 1.0 mL of each con-
centration was used for the study. To this, 9.0 mL of
Lowenstein-Jensen medium was added. A sweep from
M. tuberculosis H37RV strain culture was discharged with
the help of nichrome wire loop with a 3 mm external
diameter into a vial containing 4 mL of sterile DW. The
vial was shaken for 5 min. Then using nichrome wire loop
suspension was inoculated on the surface of each of
Lowenstein-Jensen medium containing the test com-
pounds. Further test media was incubated for 28 days at
37 °C. Readings were seen after 28 days of incubation.
The appearance of turbidity was considered as bacterial
growth and indicates resistance to the compound. Test
compounds were compared to reference drugs isoniazid,
ethambutol, and streptomycin. Lowenstein-Jensen med-
ium containing standard drugs was inoculated with
M. tuberculosis H37RV strain. Anti-tubercular activity test
was run in triplicate and the deviation for any triplicate
results was not more than 1–5 % and results are sum-
marized in Table 3.
Preparation of solution
a) Acetate buffer, 300 mM pH 3.6 (3.1 g sodium acetate
trihydrate and 16 ml concentrated acetic acid per L of
buffer solution).
b) 10 mM 2,4,6-tripyridyl-s-triazine (TPTZ) (MW 312.34)
in 40 mM HCl.
c) 20 mM FeCl3ꢀ6H2O (MW 270.30) in DW.
d) 1 mM of ascorbic acid (MW 176.13 g mol-1) dis-
solved in 100 mL DW.
FRAP working solution: mix the above prepared (a), (b),
and (c) solutions in the ratio of 10:1:1, respectively. A
mixture of 40.0 lL, 0.5 mM sample solution, and 1.2 mL
FRAP reagent was incubated at 37 °C for 15 min. Working
solution must be always freshly prepared. The ascorbic
acid was used as a standard anti-oxidant compound.
In vitro evaluation of anti-tuberculosis activity
An entitle compounds were evaluated for in vitro anti-
tubercular activity. The MICs were determined and
123

Med Chem Res
Table 3 Anti-tuberculosis activity of synthesized compounds
CuðNO3Þ2ꢀ3H2O þ L
MIC lg mL-1 M. tuberculosis
(MTCC 200)
% Inhibition
þ CQ ꢁ! dil: NaOH½CuðLÞðCQÞðH2OÞðOHÞꢂ
þ 2NaNO3 þ xH2O
where L = L1, L2, L3, L4, L5, L6.
Entry
L1
100
100
50
18
23
46
88
54
37
21
29
52
96
92
43
98
99
99
L2
IR spectra
L3
L4
12.5
50
The important infrared spectral bands and their tentative
assignments for the synthesized compounds were recorded
as KBr disks and are summarized in Table 4. The IR data of
free ligands and its metal complexes were carried out within
the IR range 4,000–400 cm-1. In 8-hydroxyquinoline
complexes of divalent metals, (C–O) band appeared at
*1,120 cm-1 region and position of the band slightly varies
with the metal (Charles et al., 1956), furthermore (C–O)
peak observed in free oxine molecule at *1,090 cm-1
which shifted to higher frequencies in all mixed-ligand
complexes giving a strong absorption band at *1,110 cm-1
L5
L6
50
C1
100
[50
25
C2
C3
C4
3.125
12.5
25
C5
C6
,
Streptomycin
Isoniazid
Ethambutol
6.25
0.25
3.125
.
This clearly indicates that 8-hydroxyquinoline has been
affected to leading complexation through metal ion. The IR
spectrum of the ligands L2 and L3 shows a strong –OH
stretching band between 3,350 and 3,400 cm-1, while
spectra of mixed-ligand Cu(II) complexes indicates a broad
band in the region 3,300–3,500 cm-1 due to stretching
vibration of OH group which revels formation of complexes
and other bands at *850 and *715 cm-1 due to rocking
and wagging vibration of the water molecule and OH group,
respectively (Nakamoto, 2009). In addition, IR spectra of the
coumarin derivatives [L1–L6] shows 1,610 and 1,743 cm-1
bands corresponding to a, b-unsaturated ketone and lactone
carbonyl ketone, respectively, upon complexation these
peaks shifted to a lower frequency 1,600 and 1,700 cm-1
due to complex formation. Moreover, weak bands around
519 cm-1 (Patel et al., 2011) and 776 cm-1 (Tu¨mer et al.,
1999) are attributed to Cu–O and Cu–N stretching fre-
quency, respectively. Tumer et al. mentioned that week band
around 500 and 770 cm-1 were attributed to the Cu–O and
Cu–N stretching frequency (Tu¨mer et al., 1999).
Results and discussion
The properties of Cu(II) complexes with coumarin deriva-
tives were studied. The synthesized compounds were char-
acterized and discussed on the basis of elemental analysis,
infrared spectra, electronic spectra, FAB mass spectroscopy,
thermal methods, magnetic and kinetic measurements.
Further anti-microbial, anti-tuberculosis, and anti-oxidant
activities for the same compounds were discussed.
Elemental analysis
Analytical and physicochemical data of the complexes are
summarized in Table 1. The complexes are colored and
stable in air. They are insoluble in water and in most organic
solvents but partially soluble in DMF as well as DMSO. The
structure of the complexes is assumed according to the
chemical reaction as shown below:
Table 4 FT-IR data of the complexes
Complexes (C1–C6) m(O–H)br (cm-1
)
m(C=N)w (cm-1
)
a, b-unsaturated Lactone carbonyl m(Cu–N)w (cm-1
)
m(Cu–O)w (cm-1
)
m(C=O)s (cm-1
)
m(C=O)s (cm-1
)
C1
C2
C3
C4
C5
C6
3,375
3,350
3,355
3,400
3,385
3,410
1,565
1,575
1,570
1,560
1,570
1,565
1,604
1,600
1,605
1,600
1,602
1,600
1,710
1,700
1,710
1,705
1,725
1,715
750
770
760
765
770
750
505
500
505
495
490
500
s strong, w weak, br broad
123

Med Chem Res
FAB spectra
configuration. The observed magnetic moments of all
complexes correspond to characteristic high-spin octahe-
dral complexes. However, these values are slightly higher
than the expected spin-only values due to spin–orbit cou-
pling contribution (Cotton, 1999). Cu(II) complexes with
octahedral geometry reveals that the absorption spectra are
in visible region and only one broad band about 615 nm
(Lewis et al., 1960; Patel et al., 2010). Here in the case of
our spectra the only kmax was found at about 615 nm which
indicated an octahedral geometry for metal complexes.
The fast atom bombardment (FAB) mass spectra of all
complexes were obtained using m-nitrobenzyl alcohol as
matrix. FAB-mass spectra of complexes and its fragmen-
tation scheme of the complex C1 (C31H21ClCuINO6) given
in supplementary material. This spectrum reveals that
molecular ion peak at m/z 727 of complex (without water
of crystallization) along with several other peaks observed
at 710, 583, 531, 440, 389, 349, 324, 280, 147, and 146
m/z value. Thus, the m/z of all fragments of complex with
relative intensity confirms the stoichiometry of complex.
Apart from it several peaks found at 136,137,154, and
307 m/z value are due to the usage of matrix.
Thermal studies of Cu(II) complexes
Thermal decomposition data of all complexes are summa-
rized in Tables 5 and 6. Thermogravimetric analysis (TG
and DTG) representative curves corresponding to complex
(C2) are presented in Figs. 1 and 2. Thermal decomposition
occurs in three steps. In first step, endothermic decomposi-
tion between 180 and 240 °C attributed to dehydration
process, which is due to loss of coordinated water molecule
and hydroxyl ion among which the observed mass loss is
4.62 %, which is nearly equal to theoretical value 4.70 %.
Loss of coordinated water molecule and hydroxyl ion is a
first-order and value of energy of activation for dehydration
Reflectance spectra and magnetic properties
The magnetic moments of mixed-ligand Cu(II) complexes
(d9 system) are known for their varieties of structures due
to their various coordination numbers. Six coordinated
Cu(II) complexes possess distorted octahedral geome-
try. Magnetic moments of the Cu(II) complexes lies in
between 1.87 and 1.97 BM range. These values are typical
of mononuclear Cu(II) compounds with d9 electronic
Table 5 Thermo analytical data of Cu(II) complexes
Complexes [formula]/(code)
TG range (°C)
DTGmax (°C)
Mass loss/% obs. (calculated)
Assignment
[Cu(L1)(CQ)(H2O)(OH)]
190–250
280–380
380–800
232
354
529
4.49 (4.81)
41.62
Removal of 1 mol –OH and H2O
Removal of L1 ligand
(C1)
39.32
Removal of CQ ligand
Leaving CuO residue
14.57
[Cu(L2)(CQ)(H2O)(OH)]
180–240
290–380
380–800
229
352
535
4.62 (4.70)
39.69
Removal of 1 mol –OH and H2O
Removal of L2 ligand
(C2)
43.32
Removal of CQ ligand
Leaving CuO residue
12.37
[Cu(L3)(CQ)(H2O)(OH)]
170–220
280–360
360–800
227
355
537
4.94 (4.70)
42.29
Removal of 1 mol –OH and H2O
Removal of L3 ligand
(C3)
41.23
Removal of CQ ligand
Leaving CuO residue
11.54
[Cu(L4)(CQ)(H2O)(OH)]
180–250
280–390
390–800
235
353
532
4.39 (4.59)
44.23
Removal of 1 mol –OH and H2O
Removal of L4 ligand
(C4)
39.36
Removal of CQ ligand
Leaving CuO residue
12.02
[Cu(L5)(CQ)(H2O)(OH)]
200–260
260–370
370–800
225
339
533
4.92 (4.53)
43.33
Removal of 1 mol –OH and H2O
Removal of L5 ligand
(C5)
39.23
Removal of CQ ligand
Leaving CuO residue
12.52
[Cu(L6)(CQ)(H2O)(OH)]
160–230
260–390
390–800
225
359
552
4.39 (4.53)
43.63
Removal of 1 mol –OH and H2O
Removal of L6 ligand
(C6)
39.22
Removal of CQ ligand
Leaving CuO residue
12.76
123

Med Chem Res
Table 6 Kinetic parameters of Cu(II) complexes
Complex [formula]/(code) TG range (°C) Ea (kJ mol-1
)
n
A (s-1
)
S* (J K-1 mol-1
)
H* (kJ mol-1 -1
)
G* (kJ mol-1
)
[Cu(L1)(CQ)(H2O)(OH)]
190–250
280–380
380–800
180–240
290–380
380–800
170–220
280–360
360–800
180–250
280–390
390–800
200–260
260–370
370–800
160–230
260–390
390–800
3.45
15.49
74.84
3.81
1.00 0.012
1.30 0.164
0.97 7.12 9 102
-104.3
-99.27
-97.63
-102.93
-97.46
-95.16
-101.3
-97.46
-96.57
-109.51
-96.52
-90.6
0.163
19.84
67.55
0.154
15.45
64.48
0.147
12.76
61.72
0.176
19.69
63.59
0.191
21.763
54.641
0.175
13.25
60.96
31.53
42.73
(C1)
176.89
37.78
[Cu(L2)(CQ)(H2O)(OH)]
1.03 0.067
(C2)
18.11
72.57
3.57
1.12 0.135
1.17 7.25 9 102
45.44
157.07
35.75
[Cu(L3)(CQ)(H2O)(OH)]
1.05 0.024
(C3)
14.21
67.27
3.78
1.27 0.113
1.12 7.45 9 102
43.18
152.43
36.27
[Cu(L4)(CQ)(H2O)(OH)]
0.99 0.065
(C4)
19.65
73.29
3.34
1.19 0.174
1.12 7.32 9 102
42.76
163.97
36.634
48.374
167.476
33.72
[Cu(L5)(CQ)(H2O)(OH)]
1.15 0.041
-105.5
-98.78
-93.26
-102.3
-98.14
-97.17
(C5)
16.67
64.53
3.51
1.20 0.125
1.00 7.74 9 102
[Cu(L6)(CQ)(H2O)(OH)]
1.10 0.023
(C6)
20.82
76.17
1.32 0.165
1.02 7.63 9 102
42.76
152.25
process is found to be 3.81 kJ mol-1. In second step, exo-
thermic decomposition between 290 and 380 °C corre-
sponds to loss of coordinated ligand with observed mass loss
39.69 %. Next step was also exothermic and associated with
elimination of coordinated CQ, respectively. As temperature
increases (380–800), intermediate complexes [Cu(CQ)]
converted to CuO residue of fragments. Observed mass loss
in this step is 43.32 %. Final product estimated as CuO, has
observed mass of 12.37 % compared to the calculated value
of 10.61 %. First is dehydration process with endothermic
effect on DTG curve at 229 °C, while increase in the tem-
perature of [Cu(L2)(CQ)], shows exothermic effect at
352 °C in second step. In third step, exothermic DTG peak at
535 °C is associated with elimination of CQ. Final residue
predicted as CuO, while thermal fragmentation scheme for
[Cu(L2)(CQ)(H2O)(OH)] is shown in Scheme 3.
Kinetic measurement and thermal stability
In past decade there has been major interest in determining
rate-dependent parameters of solid-state non-isothermal
decomposition reactions by analysis of TG curves. A
ˇ
number of equations (Sestak et al., 1973; Wendlandt, 1974)
´
have been reported to analyze a TG curve and to obtain
ˇ
´
values for kinetic parameters. Wendlandt et al. (Sestak
et al., 1973; Wendlandt, 1974) has discussed advantages of
this method over the conventional isothermal method. Rate
Fig. 1 TG curve of the
complex C2
123

Med Chem Res
Fig. 2 DTG curve of the
complex C2
Scheme 3 Thermal
fragmentation of complex C1
of a decomposition process can be described as product of
two separate functions of temperature and conversion
respectively, where h is the Plank constant, A is the heating
rate, K is the Boltzmann constant, and Ts is temperature of
peak for DTG curve. Each compound (C1–C6) has fol-
lowed decomposition process as shown below
ˇ
´
(Sestak et al., 1973). Some of the kinetic parameters such
as activation energy and order of reaction for initial
decomposition reaction were calculated and relationship
between thermal stability and chemical structure of com-
plexes is discussed. Commonly used methods for this
purpose are differential method of Freeman and Carroll
(1958) integral method of Coats and Redfern (Refat et al.,
2008) and the approximation method of Horowitz and
Metzger (Refat et al., 2008).
Solid ꢁ 1 ! Solid ꢁ 2 þ Gas
All complexes were evaluated for their thermally active
parameters (Ea and n) of decomposition process using
following equation:
½ðꢁEa=2:303RÞDð1=TÞꢂD log wr
¼ ꢁn þ ½D logðdw=dtÞ=D log wrꢂ
In our investigation, thermal behaviors of all complexes
in terms of stability, peak temperatures, and values of
kinetic parameters were investigated. Kinetic parameters of
decomposition method such as entropy (S*), enthalpy (H*),
pre-exponential factor (A), and Gibbs free energy (G*)
were studied using the Horowitz-Metzger equation method
and discussed in brief as below. Results obtained by this
method are well-correlated with each other and are sum-
marized in Table 6. The pre-exponential factor (A) was
calculated from the equation: Ea/RT2s = A/A exp (-Ea/
RTs). The entropy (S*), enthalpy (H*), and Gibbs free
energy (G*), were calculated from: S* = 2.303(log Ah/
KTs) R, H* = Ea - RTs* and G* = H* - Ts S*
where R is gas constant, T is temperature in K, wr = wc - w;
wc is the mass loss at completion of reaction, and w is total
mass loss up to time t. Ea and n are energy of activation and
order of reaction, respectively. The method reported by
Freeman and Carroll (1958) has been assumed. Plots of
½d logðdw=dtÞ=d log wrꢂ versus ½dð1=TÞ=d log wrꢂ were lin-
ear for all decomposition steps. Energy of activation Ea was
calculated from slopes of these plots for all stages and order
of reactions (n) determined from intercept, which shows
first-order reaction over whole range of decomposition for
all complexes. A typical plot for thermal degradation
of [Cu(L2)(CQ)(H2O)(OH)] is shown in (Fig. 3). All
123

Med Chem Res
than that of ampicillin. Majority of the complexes showed
parallel inhibitory action compared to standard ampicillin.
Reviewing of the anti-fungal activity indicated that all the
compounds have exhibited good activity against A. niger
and C. albicans compared to standard fungicidal nystatin.
As per results, the comparative study between ligands and
their complexes showed increase in the activity of all the
complexes than ligands due to their coordination to metal.
Furthermore, complex C2 having 3-hydroxy substitution
on phenyl ring have been found activity (100 lg mL-1
)
against E. coli and (200 lg mL-1) against B. subtilis but
changing the position of hydroxyl group to 4-position of
phenyl ring (complex C3), resulted increase the activity
towards E. coli (70 lg mL-1) and B. subtilis (100 lg mL-1).
Similar situation observed in case of complex C6 carrying
nitro substitution on phenyl ring at 2-position have been found
moderate activity against all bacterial species. While,
replacing the 2-position of nitro group to 4-position of phenyl
ring(complexC5), resultedincreasetheanti-bacterialpotency
towards all bacterial species. It has been observed that the
complexes having substitution at 4-position on phenyl ring
showed better anti-microbial potency than substitution at
other position.
Fig. 3 Thermal degradation plot of complex C2
complexes have negative entropy according to the kinetic
data obtained from DTG curves specify that synthesized
complexes have higher controlled systems than reactants and
are stable (Refat et al., 2008) also higher activation energy
reveal the high stability of such complexes due to their
covalent bond character (Hatakeyama and Quinn, 1999;
Olomola et al., 2010). The improved stability of the benzo-
coumarin metal complexes showed a correlation with
increased anti-microbial activity.
Interestingly, the complexes C4 and C5 with electron
negative groups at 4-position on the phenyl ring displayed
excellent inhibitory action against most of the employed
strains than (un)substitutions (C1) and electron donating
group at 3 and 4-position (C2 and C3) on the phenyl ring.
The complexes C4 and C5 have been found as leading anti-
microbial members against most of the employed stains.
Thus from the data obtained, the potency order on the basis
of various substitutions on the phenyl ring is given as
4-Cl [ 4-NO2 [ 4-OH [ 3-OH = –H [ 2-NO2.
Anti-microbial
All synthesized compounds were evaluated for their anti-
microbial activity against various microorganisms such as
E. coli, P. aeruginosa, S. pyogenes, B. subtilis, A. niger, and
C. albicans using Kirby-Bauer disk diffusion method and
results were compared with standard drugs as summarized
in Table 2. Fursina et al. have suggested that the transition
metal complexes with biologically active ligands frequently
exhibit higher biological activity and lower toxicity than
initial ligands, which makes possible their use in medicine
and biochemistry (Fursina et al., 2002). Raman et al. have
reported that complex exhibit higher anti-microbial activity
than free ligands (Raman et al., 2003). An increased activity
of metal chelates can be explained on the basis of chelation
theory (Raman et al., 2009) according to which polarities
(Keshavan and Gowda, 2002; Srivastava, 1981) of ligands
and central metal atoms are reduced through charge equil-
ibration over whole chelate ring. This increases lipophilic
character of metal chelate and favors its permeation through
lipid layer of bacterial membranes (Varnes et al., 1972). As
shown in Table 2, all complexes possessed good to better
activity against bacterial and fungal species. Compounds
C3, C4, and C5 have found excellent activity compared with
standard drug ampicillin against E. coli as well as against
P. aeruginosa, compound C4 showed better activity com-
pared to standard drug. In Gram-positive bacteria, com-
pounds C4 and C5 towards S. pyogenes as well as compound
C4 towards B. subtilis displayed superior inhibitory action
Anti-oxidant
In vitro anti-oxidant activity of complexes C1–C6 was
measured using FRAP assay and results expressed in mM
of ascorbic acid per 100 g of sample (Table 2), exposed
moderate to good activity. Among the all test compounds,
hydroxyl group substituted derivatives posses more ferric-
reducing power compared to that of chloro, nitro or
unsubstituted one. Thus from the data obtained, potency
order is given on basis of various substitutions attached to
phenyl ring as –OH [ –NO2 [ –H [ –Cl. However, all
the complexes have been found to show significant activity
compared to the standard ascorbic acid.
Anti-tubercular activity
The anti-tubercular activities of all the synthesized com-
pounds were assessed against M. tuberculosis H37RV at
different concentration 3.125, 6.25, 12.5, 25, 50, and
123

Med Chem Res
100 lg mL-1. The MIC of test compounds compared with
standard drugs Isoniazid, Ethambutol, and Streptomycin as
well as % inhibition are summarized in Table 3. Ligands
show inhibition concentrations 100 and 50 lg mL-1 except
L4 12.5 lg mL-1. A complex C1 also exhibits activity at
100 lg mL-1 concentration, while C4 and C5 complexes
have shown enhancement in activity with MIC of 3.125 and
12.5 lg mL-1 along 96 and 92 %, respectively, where other
complexes exhibits at 25 lg mL-1 as MIC. Compound C4
has been emerged as the promising anti-tubercular member
due to better activity along with compared to streptomycin.
Albano CL, Sciamanna R, Aquino T, Martinez JJ (2000) European
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Andrew JM (2001) In vitro susceptibility of ertapenem by BSAC
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Bedoya LM, Beltran M, Sancho R, Olmedo DA, Sanchez-Palomino S,
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(2005) 4-Phenylcoumarins as HIV transcription inhibitors. Bioorg
Med Chem Lett 15:4447–4450
Bischler A (1892) Chem Ber 25:2860
Burdette SC, Lippard SJ (2003) Proc Natl Acad Sci USA 100:3605
Carrasco F (1993) The evaluation of kinetic parameters from thermo-
gravimetric data: comparison between established methods and the
general analytical equation. Thermochim Acta 213:115–134
Charles RG, Freiser H, Friedel R, Hilliard LE, Johnston WD (1956)
Infra-red absorption spectra of metal chelates derived from
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8-hydroxyquinoline. Spectrochim Acta 8:1–8
Conclusion
Clinical and Laboratory Standards Institute (Clsi) (formerly Nccls)
(2006) Performance standards for antimicrobial disk suscepti-
bility tests approved standard M-A. Clinical and Laboratory,
Standards Institute, Wayne
The synthesized Cu(II) complexes are confirmed based on
the data obtained from physico-chemical, spectroscopic,
magnetic and thermal properties. TG curves of complexes
shows weight loss of 4.6 % in temperature range 180–
250 °C may be assigned to coordinated hydroxyl ion and
water molecule. Structures for all metal complexes suggest
octahedral geometry in which 1,3-diketone and eneamino
linkage of ligands are OOON donors to metal. Further-
more, the geometry was confirmed using electronic spectra
and magnetic moment value. Anti-microbial studies
revealed that the metal complexes are more effective than
that of relevant free ligands. Apart from this, compounds
C4 and C5 showed excellent activity compared with stan-
dard drugs while other compounds exhibit good to mod-
erate activity against all bacteria. In review, the complexes
C4 and C5 have been found as leading anti-microbial
members against most of the employed stains due to the
complexes having electron negative groups at 4-position on
the phenyl ring. In vitro anti-tubercular activity of all
synthesized compounds shows good results with an
enhancement of activity on complexation among metal
ions. Especially, compound C4 has been emerged as the
hopeful anti-tubercular member due to excellent activity
along with compared to streptomycin, while good anti-
oxidant power was shown by complexes as compared to
ascorbic acid.
¨
¨
¨ ¨
Colak A, Terzi U, Col M, Karaoglu S¸A, Karabocek S, Kuc¸ukdumlu
A, Ayaz FA (2010) DNA binding, antioxidant and antimicrobial
activities of homo- and heteronuclear copper(II) and nickel(II)
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providing instrumental facilities.
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